Background <p>The Cardiovascular-Kidney-Metabolic (CKM) syndrome framework acknowledges metabolic dysfunction-associated steatotic liver disease (MASLD) as a major manifestation, yet hepatic involvement remains insufficiently incorporated into risk stratification. This review proposes the metabolic disorder-MASLD-cardiovascular disease-kidney disease (MMCK) syndrome as an operational extension that integrates hepatic fibrosis assessment into cardiometabolic-renal care.</p> Methods <p>We conducted a comprehensive narrative review across PubMed/MEDLINE, Embase, Web of Science, Cochrane Library, and Scopus through March 2026. We synthesized evidence on pathophysiological crosstalk, proposed the Multi-Organ Risk Score (MORS)-enabled MMCK staging criteria (Stages 0–4), and developed stage-specific management algorithms.</p> Results <p>The MMCK framework introduces four key operational advances: (i) quantitative multi-organ risk stratification through the MORS (L + C + B + K, range 0–12) with mandatory FIB-4/VCTE-based hepatic fibrosis assessment as the L-Score; (ii) stage-specific therapeutic thresholds linked to objective clinical cutoffs; (iii) a structured multidisciplinary team governance model with MORS-based electronic health record triggers; and (iv) a three-tiered endpoint framework for quality improvement and prospective validation. Observational evidence indicates that incorporating MASLD fibrosis into cardiometabolic staging improves coronary artery disease risk prediction. The MMCK framework positions MASLD as a cardiovascular risk-modifying axis within established cardiometabolic-renal care.</p> Conclusions <p>The MMCK syndrome operationalizes hepatic integration within established cardiometabolic-renal care by providing a quantitative, stage-specific framework for multi-organ risk assessment and management. Future research should prospectively validate MORS-based staging in diverse cohorts and evaluate whether MMCK-guided management improves clinical outcomes compared with CKM-guided care alone.</p>

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Metabolic disorder-MASLD-cardiovascular disease-kidney disease (MMCK) syndrome: an expansion of the Cardiovascular-Kidney-Metabolic (CKM) framework

  • Yan Guo,
  • Ying Zhang,
  • Suxuan Liu,
  • Dajin Zou

摘要

Background

The Cardiovascular-Kidney-Metabolic (CKM) syndrome framework acknowledges metabolic dysfunction-associated steatotic liver disease (MASLD) as a major manifestation, yet hepatic involvement remains insufficiently incorporated into risk stratification. This review proposes the metabolic disorder-MASLD-cardiovascular disease-kidney disease (MMCK) syndrome as an operational extension that integrates hepatic fibrosis assessment into cardiometabolic-renal care.

Methods

We conducted a comprehensive narrative review across PubMed/MEDLINE, Embase, Web of Science, Cochrane Library, and Scopus through March 2026. We synthesized evidence on pathophysiological crosstalk, proposed the Multi-Organ Risk Score (MORS)-enabled MMCK staging criteria (Stages 0–4), and developed stage-specific management algorithms.

Results

The MMCK framework introduces four key operational advances: (i) quantitative multi-organ risk stratification through the MORS (L + C + B + K, range 0–12) with mandatory FIB-4/VCTE-based hepatic fibrosis assessment as the L-Score; (ii) stage-specific therapeutic thresholds linked to objective clinical cutoffs; (iii) a structured multidisciplinary team governance model with MORS-based electronic health record triggers; and (iv) a three-tiered endpoint framework for quality improvement and prospective validation. Observational evidence indicates that incorporating MASLD fibrosis into cardiometabolic staging improves coronary artery disease risk prediction. The MMCK framework positions MASLD as a cardiovascular risk-modifying axis within established cardiometabolic-renal care.

Conclusions

The MMCK syndrome operationalizes hepatic integration within established cardiometabolic-renal care by providing a quantitative, stage-specific framework for multi-organ risk assessment and management. Future research should prospectively validate MORS-based staging in diverse cohorts and evaluate whether MMCK-guided management improves clinical outcomes compared with CKM-guided care alone.